Comparison of Acute Toxicities, Overall Treatment Time and Quality of Life in Head and Neck Cancer Patients Treated with IMRT and Helical Tomotherapy.

INTRODUCTION: Technical innovations in radiation therapy treatment planning and delivery over the last two decades have changed the practice of radiation therapy dramatically. The benefit of improved dose homogeneity and better sparing of critical structures in helical tomotherapy compared with conventional linac-based IMRT has been reported. This study was conducted to compare acute toxicities (skin, mucous membrane, salivary gland and hematological) during treatment and overall treatment time in Head and Neck Cancer patients treated with IMRT and Helical Tomotherapy and to assess the quality of life of patients during treatment between two groups. MATERIALS AND METHODS: The study involved thirty patients with histologically proven Squamous cell carcinomas of Head and Neck. They were treated with concurrent chemoradiotherapy, to a dose of 60-70 Gray in 30-35 fractions. The study consists of 2 arms which are standard IMRT and Tomotherapy arm. Fifteen consecutive patients were treated under IMRT and 15 patients were treated under Helical tomotherapy, along with concurrent chemotherapy. After completion of planning, plans were evaluated and dose to the targets, organs at risk were tabulated. Patients were assessed weekly for acute toxicities (skin reactions, mucositis, xerostomia, haematological toxicities) during the course of the treatment as per RTOG criteria. Quality of life of patients were assessed using FACT/ NCCN HNSI questionnaire in local language at day 1, day 21 and at completion of radiotherapy. RESULTS: Grade 2-3 skin reactions, mucositis, anemia, leukopenia and thrombocytopenia were predominant in both arms. Treatment time from start of radiotherapy to completion of radiotherapy varied from 39 days to 68 days. Majority of patients completed radiotherapy within 50-56 days. Mean quality of life score did not show much difference between IMRT and tomotherapy arms. CONCLUSION: The study did not show any statistically significant difference in overall treatment time, acute toxicities- skin reactions, xerostomia, mucositis& hematological toxicities and quality of life of patients during radiotherapy between IMRT and Helical Tomotherapy. Dosimetric benefits of Tomotherapy over IMRT do not translate into clinical benefit in terms of reduced acute toxicities, lesser overall treatment time and better quality of life of patients. KEY WORDS: Head and Neck Carcinoma, IMRT, Tomotherapy, RTOG, toxicity, FACT/ NCCN HNSI, quality of life.

Therapeutic In Situ Cancer Vaccine Using Pulsed Stereotactic Body Radiotherapy-A Translational Model.

Both radiation and cancer therapeutic vaccine research are more than 100 years old, and their potential is likely underexplored. Antiangiogenics, nanoparticle targeting, and immune modulators are some other established anticancer therapies. In the meantime, immunotherapy usage is gaining momentum in clinical applications. This article proposes the concept of a pulsed/intermittent/cyclical endothelial-sparing single-dose in situ vaccination (ISVRT) schedule distinguishable from the standard therapeutic stereotactic body radiotherapy (SBRT) and stereotactic radiosurgery (SRS) plans. This ISVRT schedule can repeatedly generate tumor-specific neoantigens and epitopes for primary and immune modulation effects, augment supplementary immune enhancement techniques, activate long-term memory cells, avoid extracellular matrix fibrosis, and essentially synchronize with the vascular normalized immunity cycle. The core mechanisms of ISVRT impacting in situ vaccination would be optimizing cascading antigenicity and adjuvanticity. The present proposed hypothesis can be validated using the algorithm presented. The indications for the proposed concept are locally progressing/metastatic cancers that have failed standard therapies. Immunotherapy/targeted therapy, chemotherapy, antiangiogenics, and vascular-lymphatic normalization are integral to such an approach.

Vascular normalization and immunotherapy: Spawning a virtuous cycle.

Anti-angiogenics, radiotherapy (especially stereotactic body radiotherapy, SBRT)/chemotherapy, and immunotherapy form a critical trimodal approach in modern cancer therapy. The normalization window, however short, is the beachhead for the strategic initiation of a decipherable disruption of cancer cells. This opening can be the opportunity for designing controlled stepwise cancer cell death (CCD) and immunological augmentation. The next step is to induce immunogenic cell death (ICD) through chemotherapy/radiotherapy concurrently with the facilitation of professional phagocytosis. Immunotherapy at this stage, when interstitial pressure decreases considerably, leads to the improved perfusion of oxygen with solutes and improved immune-friendly pH and is additionally expected to open up the tumor microenvironment (TME) for a "flood" of tumor-infiltrating lymphocytes. Furthermore, there would be enhanced interaction in "hot" nodules and the incorporation of immune reaction in "cold" nodules. Simultaneously, the added adjuvant-assisted neoantigen-immune cell interaction will likely set in a virtuous cycle of CCD induction followed by tumor cell-specific antigenic reaction boosting CCD, in turn promoting the normalization of the vasculature, completing the loop. There should be a conscious concern to protect the extracellular matrix (ECM), which will nurture the long-term immunological cross-talk to discourage dormancy, which is as essential as obtaining a complete response in imaging. The caveat is that the available therapies should be appropriately ranked during the start of the treatment since the initial administration is the most opportune period. A fast-paced development in the nanomedicine field is likely to assist in all the steps enumerated.

Stereotactic Body Radiotherapy Immunological Planning-A Review With a Proposed Theoretical Model.

In the stereotactic body radiotherapy (SBRT) and immunotherapy era, we are moving toward an "immunological radiation plan", i.e., radiation scheduling with abscopal effect as a vital endpoint as well. The literature review of part A enumerates the advantages of the intermediate dose of SBRT 6-10 Gy per fraction, appropriate use of dose painting, proper timing with immunotherapy, and the potential of immunoadjuvants to maximize cell kill in the irradiated lesions, found to have improved the abscopal effects. Part B summarizes part A, primarily the findings of animal trials, forming the basis of the tenets of the proposed model given in part C to realize the true abscopal potential of the SBRT tumor cell kill of the index lesions. Part C proposes a theoretical model highlighting tumor vasculature integrity as the central theme for converting "abscopal effect by chance" to "abscopal effect by design" using a harmonized combinatorial approach. The proposed model principally deals with the use of SBRT in strategizing increased cell kill in irradiated index tumors along with immunomodulators as a basis for improving the consistency of the abscopal effect. Included is the possible role of integrating immunotherapy just after SBRT, "cyclical" antiangiogenics, and immunoadjuvants/immune metabolites as abscopal effect enhancers of SBRT tumor cell kill. The proposed model suggests convergence research in adopting existing numerous SBRT abscopal enhancing strategies around the central point of sustained vascular integrity to develop decisive clinical trial protocols in the future.

Vascular-immuno-phenotypic (VIP) model for locally advanced and oligo-metastatic cancer: A hypothesis.

Primary Hypothesis: In cancer therapy, normalization of the vasculature, and not disruption, to facilitate the reversal of the immuno-phenotypic changes, is the sine-qua-non for cancer elimination. The triad of normalization of the vasculature, leading to the improved immunological tumour microenvironment and increased susceptibility of resistant phenotypic cancer cells (VIP model), forms the basis of this hypothesis. This article hypothesizes the absolute need for vascular normalization for the eradication of cancer. Locally advanced and oligometastatic cancers have the potential to be cured with aggressive therapy. The focus on vascular normalization its clinical relevance in this situation is essential. Most traditional approaches have focused on the elimination of cancer by targeting and disrupting vasculature. Initially, antiangiogenic drugs showed significant promise in animal experiments. However, this vascular disruption approach has not paid the expected long-term dividends in the clinical setup. However, antiangiogenics are playing a significant role when used concurrently with chemotherapy/immunotherapy. Antiangiogenics have dual temporal actions - an initial normalization effect with improved oxygenation followed by pruning of blood vessels, resulting in exaggerated hypoxia along with a rebound progression. The literature is replete with phenomena of initial vascular normalization with a paradigm shift in the immuno-phenotypic milieu of cancer as part of vascular targeting approaches. The hypothesis in this article stresses the need to have strategies to extend this normalization window or to have pre-clinical trials to optimize the dose scheduling of antiangiogenics cyclically along with chemo/targeted/immune therapy and other combination therapies. We can implement this hypothesis by a combinatorial harmonization of present-day cancer therapies in the setting of tumor vasculature integrity. In addition, based on the proposed hypothesis, the current normalization effect of antiangiogenics and newer therapy development should focus primarily on normalization of the vasculature as well as targeting hypoxia-Inducible-factor-1 alpha (HIF-1 α) in the presence of differential genetic modulation of vascular endothelial cell resistance enhancement along with cancer cell sensitization. Also, the article enumerates six supporting hypotheses supplementing the primary hypothesis.

Decreased Survival With Mastectomy Vis-à-Vis Breast-Conserving Surgery in Stage II and III Breast Cancers: A Comparative Treatment Effectiveness Study.

PURPOSE: The primary purpose of hospital-based cancer registries is assessing patient care. Clinical stage-based survival and treatment-based survival are some of the key parameters for such assessment. Because of the challenges in obtaining follow-up parameters, a separate study on patterns of care and survival was undertaken by the Indian National Cancer Registry Program. The results for cancer of the female breast are presented here. PATIENTS AND METHODS: Data abstracted in a standardized patient information form were transmitted online to a central repository. Treatment patterns were assessed for 9,903 patients diagnosed between January 1, 2006, and December 31, 2008, from 13 institutions. Survival analysis was restricted to 7,609 patients from nine institutions wherein follow-up details (as of December 31, 2012) were available for at least 60% of patients. RESULTS: The overall 5-year survival rates with breast-conserving surgery (BCS) and mastectomy (MS) were 94.0% and 85.8%, respectively, for stage II disease (adjusted hazard ratio, 2.40; 95% CI, 1.8 to 3.2) and 87.1% and 69.0%, respectively, for stage III disease (hazard ratio, 2.82; 95% CI, 2.2 to 3.7). Patients who had MS did better with systemic therapy (chemotherapy and/or hormone therapy), whereas patients with BCS required just local radiation therapy to achieve best survival. CONCLUSION: This observational study in the natural setting of care of patients with cancer in India showed significantly decreased survival with MS when compared with BCS. The reasons for lower survival with MS and the biologic or scientific rationale of the necessity of systemic therapy to achieve optimal survival in patients undergoing MS but not in those with BCS need further investigation.

Balloon-assisted retrieval of a broken stent-delivery system.

The breakage of a stent-delivery catheter at the shaft is a rare and dangerous complication during coronary intervention. We report a simple balloon technique for the successful retrieval, from within a guiding catheter, of both an unexpanded stent and its delivery system.

Dose escalation in image-guided, intensity-modulated radiotherapy of carcinoma prostate: initial experience in India.

BACKGROUND: Increasing incidence and significant stage migration from distant metastases to a localized disease, due to screening application of PSA, is taking place in carcinoma prostate. Also, role of radiotherapy is increasing in carcinoma prostate due to rapid strides in technology. AIM: The present retrospective study, evaluates escalating the dose in the treatment of localized carcinoma prostate using integration of multiple advanced techniques. SETTINGS AND DESIGN: The settings designed are: a) use of gold seed internal fiducial markers: b) clinical application of emerging Megavoltage Cone Beam Computed Tomography (MVCBCT) technology for Image Guided Radiotherapy (IGRT); c) Intensity Modulated Radiotherapy (IMRT); d) adopting biochemical method for follow-up. METHODS AND MATERIAL: Twelve consecutive, biopsy proven localized cancer of prostate patients, treated with dose escalation IMRT & IGRT protocol between August 2006 and January 2008, were analyzed. Gold seed markers in prostate were used for daily localization with MVCBCT or Electronic Portal Imaging (EPI). All patients underwent clinical and biochemical follow-up. STATISTICAL ANALYSIS & RESULTS: Planned dose of 7740 cGy was delivered in 10 out of 12 patients (83%). While one patient had migration of maximum of 3 mm, two others had 1 mm migration of one seed during course of treatment. One patient (8%) developed Grade II proctitis at 12th month. During the mean follow-up duration of 12.2 months, 92% (11/12) had biochemical control within 3 months of treatment. CONCLUSIONS: IGRT technique using MVCBCT for implanted fiducial gold seed localization was feasible for IMRT dose escalation in carcinoma prostate with excellent results.

Dosimetric and QA aspects of Konrad inverse planning system for commissioning intensity-modulated radiation therapy.

The intensity-modulated radiation therapy (IMRT) planning is performed using the Konrad inverse treatment planning system and the delivery of the treatment by using Siemens Oncor Impression Plus linear accelerator (step and shoot), which has been commissioned recently. The basic beam data required for commissioning the system were generate. The quality assurance of relative and absolute dose distribution was carried out before clinical implementation. The salient features of Konrad planning system, like dependence of grid size on dose volume histogram (DVH), number of intensity levels and step size in sequencer, are studied quantitatively and qualitatively.To verify whether the planned dose [from treatment planning system (TPS)] and delivered dose are the same, the absolute dose at a point is determined using CC01 ion chamber and the axial plane dose distribution is carried out using Kodak EDR2 in conjunction with OmniPro IMRT Phantom and OmniPro IMRT software from Scanditronix Wellhofer. To obtain the optimum combination in leaf sequencer module, parameters like number of intensity levels, step size are analyzed. The difference between pixel values of optimum fluence profile and the fluence profile obtained for various combinations of number of intensity levels and step size is compared and plotted. The calculations of the volume of any RT structure in the dose volume histogram are compared using grid sizes 3 mm and 4 mm. The measured and planned dose at a point showed good agreement (<3%) except for a few cases wherein the chamber was placed in a relatively high dose gradient region. The axial plane dose distribution using film dosimetry shows excellent agreement (correlation coefficient >0.97) in all the cases. In the leaf sequencer module, the combination of number of intensity level 7 with step size of 3 is the optimal solution for obtaining deliverable segments. The RT structure volume calculation is found to be more accurate with grid size of 3 mm for clinical use.Thus a study regarding various aspects of commissioning of the Konrad inverse planning system for IMRT has been presented, which has been implemented in our clinic.

Sinus histiocytosis with nodal and extranodal involvement--a case report.

A two and half years old male child of sinus histiocytosis with massive lymphadenopathy, paraplegia and spinal cord involvement was treated with surgery and radiotherapy for the spinal cord compression and later with chemotherapy for his nodal disease in the neck. There was a significant improvement in his neurologic status as well as in his nodal status reiterating the role of combination therapy in this disease.